Defective release of Hepcidin not defective synthesis is the primary pathogenic mechanism in HFE-Haemochromatosis

Medical Hypotheses

Volumn 70, Issue 6, 2008, Pages 1197-1200

  Arnold, Jayantha ^a   Sangwaiya, Arvind ^a   Bhatkal, Bharati ^a   Arnold, Ahran ^a  

^a EALING HOSPITAL NHS TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FERROPORTIN; HEPCIDIN; HFE PROTEIN;

ARTICLE; GENE MUTATION; HEMOCHROMATOSIS; INTESTINE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS;

ANTI-BACTERIAL AGENTS; ANTIMICROBIAL CATIONIC PEPTIDES; HEMOCHROMATOSIS; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IRON OVERLOAD; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; MUTATION;

EID: 42949121256     PISSN: 03069877     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mehy.2007.10.007     Document Type: Article

References (23)

1. Gehrke S.G., Kulaksiz H., Herrmann T., et al. Expression of hepcidin in hereditary haemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non transferrin bound iron. Blood 102 (2003) 371-376
2. Park C.H., Valore E.V., Waring A.J., et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276 (2001) 7806-7810
3. Krause A., Neitz S., Magert H.J., et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 480 (2000) 147-150
4. Pigeon C., Ilysin G., Courselaud B., et al. A new liver specific gene encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276 (2001) 7811-7819
5. Zhang A., Xiong S., Tsukamoto H., and Enns C.A. Localisation of iron metabolism related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Blood 103 (2004) 1509-1514
6. Pietrangelo P. Hemochromatosis: an endocrine disease. Hepatology 46 (2007) 1291-1301
7. Zhang A.S., Anderson S., Meyers K.R., et al. Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through Neogenin. J Biol Chem 282 (2007) 12547-12556
8. Truksa J., Pen H., Lee P., and Beutler E. Different regulatory elements are required for response of hepcidin to interleukin 6 and bone morphogenetic proteins 4 and 9. Br J Haematol 139 (2007) 138-147
9. Walsh J.B. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol Suppl 1 (2006) S1-S8
10. Nemeth E., Valore E.V., Territo M., et al. Hepcidin, a putative mediator of anaemia of inflammation, is a type II acute phase protein. Blood 101 (2003) 2461-2463
11. Nemeth E., Roetto A., Garozo G., et al. Blood 105 (2005) 1803-1806
12. Ahmad K.A., Ahmann J.R., Migas M.C., et al. Decreased liver hepcidin expression in the HFE knockout mouse. Blood cells Mol Dis 29 (2002) 361-366
13. Bridle K.R., Fraser D.M., Wilkins S.J., et al. Disrupted hepcidin regulation in HFE associated haemochromatosis and the liver as a regulator of body iron homeostasis. Lancet 361 (2003) 669-673
14. Tomosugi N., Kawabata H., Wakatabe R., et al. Detection of serum hepcidin in renal failure and inflammation by using Proteinchip system. Blood 108 (2006) 1381-1387
15. Peysonnnaux C., Zinkermagel A.S., Datta V., et al. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 107 (2006) 3727-3732
16. Ganz T. Molecular control of iron transport. J Am Soc Nephrol 18 (2007) 394-400
17. Domenico I.D., Ward D.V., Nemeth E., et al. The molecular basis of ferroportin- linked haemochromatosis. PNAS 102 (2005) 8955-8960
18. Lesbriodes-Briton J.C., Viatte L., Bennoun M., et al. Targeted disruption of the hepcidin 1 gene results in severe haemochromatosis. Blood 108 (2006) 1402-1405
19. Roe M.A., Spinks C., Heath A.l., et al. Serum prohepcidin concentration: no association with iron absorption in healthy men: and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women. Br J Nutr 97 (2007) 544-549
20. Piperno A., Girelli D., Nemeth D., et al. Blunted hepcidin response to oral challenge in HFE haemochromatosis. Blood 110 (2007) 4096-4100
21. Robson K.J. Hepcidin and its role in iron aborption. Gut 53 (2004) 617-619
22. Franchini M. Hereditary iron Overload: Update on Pathophysiology, Diagnosis and treatment. Am J Haematology 81 (2006) 202-209
23. Kulaksiz H., Gehre S.G., Janetzko A., et al. Pro-Hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency and renal anaemia. Gut 53 (2004) 735-743